The primary goal of this proposal is the elucidation of the mechanisms of the protective effects of ovine interferon tau (IFN tau) and ovine IFN tau/human IFNalphaD chimerics in treatment of experimental allergic encephalomyelitis, an animal model of multiple sclerosis (MS). These mechanism studies involve structure studies and use of the EAE mouse model to assess the chimerics as therapeutics for treatment of MS under conditions that minimize undesirable side effects. The Specific Aims are: 1. Determination of the protective effects of ovine IFN tau/human IFNalphaD chimerics in treatment of EAE in the mouse model of MS with a focus on therapeutics efficacy versus toxic side effects. Toxic side effects are a problem in the use of type I IFNs in the treatment of MS. 2. Determination of the structural basis for the interaction of ovine IFN tau, human IFNalphaD, and chimerics of IFN tau/human IFNalphaD with the type I IFN receptor, with particular emphasis on the chimerics as it potentially relates to therapy of MS with minimal undesirable side effects. 3. Determination of the x-ray crystal structure of ovine IFN tau/human IFNalphaD chimeric and compare it to that of ovine IFN tau/human IFNalphaD, particularly with respect to the N-terminus, which may play a critical role as to whether a type I IFN is toxic or non toxic.